This paper describes the stepwise aza‐Wittig reaction of 1,1′‐bis(triphenylphosphoranylidenamino)‐ferrocene with a paramagnetic isocyanate, namely, 3‐isocyanato‐2,2,5,5‐tetramethyl‐2,5‐dihydro‐1H‐pyrrole‐1‐oxyl, and then with substituted arylisocyanates. The intermediate product (a paramagnetic betaine), which is the product of an intramolecular nucleophilic attack of the nitrogen atom of the iminophosphorane moiety on the carbon atom of the carbodiimide functional group, was isolated and structurally characterized. Subsequent interaction of the betaine with arylisocyanates under mild conditions gave spin‐labeled ferrocenophanes with the 1,3‐diazetidine‐2,4‐diimine coupler. It was found that the mutual arrangement of the substituents in the latter depends on the nature of the substituents in the arylisocyanate. Iodophenyl derivatives of 1,3‐diazetidine‐2,4‐diimines were cross‐coupled with the gold(I) nitronyl nitroxide‐2‐ide complex, thus yielding diradicals: metallocenophanes functionalized with various types of nitroxide substituents. Molecular and crystal structures of all mono‐ and diradicals were solved by X‐ray diffraction analysis.
The Cover Feature shows a beautiful sunrise metaphorically representing the boundary between chemistry and physics, the interaction of which has paved the way for the synthesis of a biradical with a ferrocene‐derived inflexible bridging moiety. This is a versatile route and could be used to prepare weakly coupled biradicals with different spin‐bearing groups and with a redox‐active ferrocene part. More information can be found in the Research Article by E. V. Tretyakov et al.
Aims: Edoxaban is a direct-acting oral anticoagulant, being a highly selective, direct and reversible factor Xa inhibitor. Edoxaban is used to treat and prevent blood clots such as deep vein thrombosis and pulmonary embolism. The dried spot technic, including dried blood spots and dried plasma spots, is used in many fields, from newborn screening to monitoring of therapeutic drugs in toxicology. In this case, equipment with a highly sensitive detector, such as a mass spectrometer, is required, as well as conditions for a high degree of drug recovery from the dried spot. In this work, the extraction of edoxaban from dried plasma spots (DPS) was studied to determine the optimal parameters of the extraction method.
Study Design: Analytical experimental study. Short Research Articles.
Place and Duration of Study: Core Facility of Mass Spectrometric Analysis, Institute of Chemical Biology and Fundamental Medicine SB RAS, between August and October 2020
Methodology: The organic extraction method was selected for evaluation as the most suitable for LC-MS analysis. Several parameters were investigated to find the best combination for extracting edoxaban from DPS for further LC-MS analysis: percent organic solvent, presence or absence of 0.1% formic acid (FA), extraction time, volume, and temperature.
Results: The results showed that the extraction was influenced by the composition and volume of the solvent, but not temperature and time. Pure acetonitrile is the worst solvent for extracting edoxaban from DPS. The most optimal parameters are MeOH: 0.1% FA in H2O (70:30, v:v) solvent with an extraction temperature of 40 °C, an extraction time of 15 minutes and a solvent volume of 50 μl.
Conclusion: Several solvents suitable for LC-MS analysis can be used to recover edoxaban from DPS.
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